Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy

J Clin Endocrinol Metab. 2015 Sep;100(9):3322-31. doi: 10.1210/jc.2015-2332. Epub 2015 Jul 20.


Context: In vitro fertilization (IVF) treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication, ovarian hyperstimulation syndrome (OHSS).

Objective: This study aimed to investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.

Setting and design: This was a phase 2, multi-dose, open-label, randomized clinical trial of 60 women at high risk of developing OHSS carried out during 2013-2014 at Hammersmith Hospital IVF unit, London, United Kingdom.

Intervention: Following a standard recombinant FSH/GnRH antagonist protocol, patients were randomly assigned to receive a single injection of kisspeptin-54 to trigger oocyte maturation using an adaptive design for dose allocation (3.2 nmol/kg, n = 5; 6.4 nmol/kg, n = 20; 9.6 nmol/kg, n = 15; 12.8 nmol/kg, n = 20). Oocytes were retrieved 36 h after kisspeptin-54 administration, assessed for maturation, and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos. Women were routinely screened for the development of OHSS.

Main outcome measure: Oocyte maturation was measured by oocyte yield (percentage of mature oocytes retrieved from follicles ≥ 14 mm on ultrasound). Secondary outcomes include rates of OHSS and pregnancy.

Results: Oocyte maturation occurred in 95% of women. Highest oocyte yield (121%) was observed following 12.8 nmol/kg kisspeptin-54, which was +69% (confidence interval, -16-153%) greater than following 3.2 nmol/kg. At all doses of kisspeptin-54, biochemical pregnancy, clinical pregnancy, and live birth rates per transfer (n = 51) were 63, 53, and 45%, respectively. Highest pregnancy rates were observed following 9.6 nmol/kg kisspeptin-54 (85, 77, and 62%, respectively). No woman developed moderate, severe, or critical OHSS.

Conclusion: Kisspeptin-54 is a promising approach to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.

Trial registration: ClinicalTrials.gov NCT01667406.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drug Therapy, Combination
  • Female
  • Fertilization in Vitro / methods
  • Follicle Stimulating Hormone / adverse effects
  • Follicle Stimulating Hormone / therapeutic use
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Hormone Antagonists / therapeutic use
  • Humans
  • Infertility, Female / therapy*
  • Kisspeptins / therapeutic use*
  • Ovarian Hyperstimulation Syndrome / chemically induced
  • Ovarian Hyperstimulation Syndrome / prevention & control*
  • Ovulation Induction / methods*
  • Pregnancy
  • Risk Factors


  • Hormone Antagonists
  • KISS1 protein, human
  • Kisspeptins
  • Gonadotropin-Releasing Hormone
  • Follicle Stimulating Hormone

Associated data

  • ClinicalTrials.gov/NCT01667406